QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 15, 2008, 28(42):10567-10575; doi:10.1523/JNEUROSCI.2457-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Satz, J. S. Articles by Campbell, K. P. Search for Related Content PubMed PubMed Citation Articles by Satz, J. S. Articles by Campbell, K. P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

 Previous Article  |  Next Article 

Neurobiology of Disease
Brain and Eye Malformations Resembling Walker–Warburg Syndrome Are Recapitulated in Mice by Dystroglycan Deletion in the Epiblast

Jakob S. Satz,^1,2 Rita Barresi,^1,2 Madeleine Durbeej,^1,2 Tobias Willer,^1,2 Amy Turner,^1,2 Steven A. Moore,³ and Kevin P. Campbell^1,2,4,5

¹Howard Hughes Medical Institute and Departments of ²Molecular Physiology and Biophysics, ³Pathology, ⁴Neurology, and ⁵Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242

Correspondence should be addressed to Kevin P. Campbell, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242-1101. Email: kevin-campbell{at}uiowa.edu

Walker–Warburg syndrome (WWS) is a severe congenital disease that is characterized by brain and eye malformations and lethality during the first year of life. Genetic mutations have been identified in a subset of WWS patients, but a majority of clinical cases have unknown etiologies. POMT1 and POMT2, two of the causative genes, form an active enzyme complex in the posttranslational biosynthetic pathway of dystroglycan. Deletion of either Pomt1 or the dystroglycan gene causes early embryonic lethality in mice. Here we report that mice with epiblast-specific loss of dystroglycan develop brain and eye defects that broadly resemble the clinical spectrum of the human disease, including aberrant neuron migration, hydrocephalus, and malformations of the anterior and posterior chambers of the eye. Breaches of basement membranes coincide with the pathology, revealing an important function for dystroglycan in the morphogenesis of the brain and eye. These findings demonstrate the central role of dystroglycan in WWS and suggest that novel defects in posttranslational processing or mutations of the dystroglycan gene itself may underlie cases in which no causative mutation has been found.

Key words: Walker–Warburg syndrome; congenital muscular dystrophy; lissencephaly; hydrocephalus; microphthalmia; dystroglycan

---

Received May 31, 2008; revised Sept. 2, 2008; accepted Sept. 3, 2008.

Correspondence should be addressed to Kevin P. Campbell, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242-1101. Email: kevin-campbell{at}uiowa.edu

This article has been cited by other articles:

				G. Nagra, L. Koh, I. Aubert, M. Kim, and M. Johnston Intraventricular injection of antibodies to {beta}1-integrins generates pressure gradients in the brain favoring hydrocephalus development in rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1312 - R1321. [Abstract] [Full Text] [PDF]

				J. S. Satz, A. R. Philp, H. Nguyen, H. Kusano, J. Lee, R. Turk, M. J. Riker, J. Hernandez, R. M. Weiss, M. G. Anderson, et al. Visual Impairment in the Absence of Dystroglycan J. Neurosci., October 21, 2009; 29(42): 13136 - 13146. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help